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Purpose: The purpose of this study was to evaluate the radiotherapy planning feasibility of dose escalation with intensity‐modulated proton therapy (IMPT) to hypoxic tumor regions identified on 18F‐Fluoromisonidazole (FMISO) positron emission tomography and computed tomography (PET‐CT) in NPC. Materials and methods: Nine patients with stages T3‐4N0‐3M0 NPC underwent 18F‐FMISO PET‐CT before and during week 3 of radiotherapy. The hypoxic volume (GTVhypo) is automatically generated by applying a subthresholding algorithm within the gross tumor volume (GTV) with a tumor to muscle standardized uptake value (SUV) ratio of 1.3 on the 18F‐FMISO PET‐CT scan. Two proton plans were generated for each patient, a standard plan to 70 Gy and dose escalation plan with upfront boost followed by standard 70GyE plan. The stereotactic boost was planned with single‐field uniform dose optimization using two fields to deliver 10 GyE in two fractions to GTVhypo. The standard plan was generated with IMPT with robust optimization to deliver 70GyE, 60GyE in 33 fractions using simultaneous integrated boost technique. A plan sum was generated for assessment. Results: Eight of nine patients showed tumor hypoxia on the baseline 18F‐FMISO PET‐CT scan. The mean hypoxic tumor volume was 3.9 cm3 (range.9–11.9cm3). The average SUVmax of the hypoxic volume was 2.2 (range 1.44–2.98). All the dose‐volume parameters met the planning objectives for target coverage. Dose escalation was not feasible in three of eight patients as the D0.03cc of temporal lobe was greater than 75GyE. Conclusions: The utility of boost to the hypoxic volume before standard course of radiotherapy with IMPT is dosimetrically feasible in selected patients. Clinical trials are warranted to determine the clinical outcomes of this approach. [ABSTRACT FROM AUTHOR]

Gels are used in the oilfield. For example, during oil recovery, organogels are pumped underground into fractures within oil‐bearing rock, so as to block fluid flow. However, after several days, the gels must be degraded (liquefied) to enable oil extraction through the fractures. To degrade gels, 'degrading agents' as well as external stimuli have been examined. Here, a concept is demonstrated that avoids external agents and stimuli: self‐degrading organogels based on the self‐assembly of molecular gelators. The gels are a) extremely robust (free standing solids) at time t = 0 and (b) degrade spontaneously into a sol after a set time t = tdegr that can be minutes, hours, or days. These properties are achieved by combining two readily available molecules — the organogelator (1,3:2,4)‐dibenzylidene sorbitol (DBS) and an acid (e.g., hydrochloric acid, HCl) — in an organic solvent. DBS self‐assembles into nanoscale fibrils, which connect into a 3‐D network, thereby gelling the solvent. The acid type and concentration set the value of tdegr at a given temperature. Degradation occurs because the acid slowly hydrolyzes the acetals on DBS, thereby converting DBS into small molecules that cannot form fibrils. DBS gels with a pre‐programmed "degradation clock" can be made with both polar and non‐polar organic solvents. The concept can be a game‐changer for oil recovery as it promises to make it safer, more efficient, and sustainable. [ABSTRACT FROM AUTHOR]

Background: The efficacy of a combination of nimotuzumab, a humanized monoclonal antibody to the epidermal growth factor receptor, with chemoradiation in locally advanced head and neck squamous cell carcinoma (HNSCC) was evaluated in a phase II study. Methods: Patients with stage III/IV HNSCC received 3‐weekly cisplatin 100 mg/m2 for three cycles and weekly nimotuzumab 200 mg for 8 weeks concurrently with radiotherapy. Primary endpoint was best overall response (BOR) and secondary endpoint was progression‐free survival (PFS). Results: Thirty‐seven patients were included; the majority were Chinese (76%), male (89%), and had stage IVA/IVB HNSCC (92%). BOR of complete and partial response was seen in 22/37 (59%) and 10/37 (27%) patients, respectively. Median PFS was 17.5 months (95% CI: 11.1–54.5) and 3‐year PFS was 40.4% (95% CI: 24.3–55.9). The frequency and type of adverse events observed were similar to standard chemoradiation. Conclusion: The combination of nimotuzumab with cisplatin and radiotherapy was safe and achieved high response rates in HNSCC. [ABSTRACT FROM AUTHOR]

Background: Lactate dehydrogenase (LDH) is a known prognostic biomarker for the endemic variant of nasopharyngeal carcinoma (NPC). Here, we investigate whether serial changes in LDH level between chemotherapy (CT) cycles are associated with tumour response to CT. Methods: Patients with biopsy-proven, recurrent or treatment-naïve metastatic NPC (mNPC) were recruited. All patients had received at least two cycles of platinum-based doublet or triplet CT, with serial assessment of LDH prior to every cycle of chemotherapy (CT1–6). Patients harbouring conditions that affect LDH levels (IU/L) were excluded. Tumour response was assessed after every two cycles of CT by RECIST v1.1. Results: A total of 158 patients were analysed, including 77 with recurrent and 81 with treatment-naïve mNPC. High pre-CT LDH was associated with an inferior overall survival [hazard ratio 1.93 for ⩾240 versus <240 (1.34–2.77), p < 0.001], which is consistent with published literature. We found that both absolute LDH levels and LDH ratios (LDHCTn: LDHCTn–1) were associated with tumour response [partial response versus progressive disease: median value across CT1–6 = 168–190 versus 222–398 (absolute); 0.738–0.988 versus 1.039–1.406 (ratio)], albeit LDH ratio had a tighter variance between patients. Finally, we showed that an LDH ratio cut-off of 1.0 at CT1, CT3 and CT5 was predictive of progressive disease at CT2, CT4, CT6 [area under the curve of 0.73 (0.65–0.80)]. Conclusion: Herein, we characterised the longitudinal variation of LDH in response to CT in mNPC. Our findings suggest the potential utility of interval LDH ratio to predict subsequent tumour response to CT. [ABSTRACT FROM AUTHOR]

Background: Inter-patient heterogeneity in radiation-induced DNA damage responses is proposed to reflect intrinsic variations in tumour and normal tissue radiation sensitivity, but the prediction of phenotype by a molecular biomarker is influenced by clinical confounders and assay reproducibility. Here, we characterised the intrapatient and inter-patient heterogeneity in biomarkers of DNA damage and repair and radiation-induced apoptosis.Methods: We enrolled 85 of 172 patients with locally advanced nasopharynx cancer from a randomised controlled phase II/III trial of induction chemotherapy added to chemo-radiotherapy. G0 blood lymphocytes were harvested from these patients, and irradiated with 1, 4, and 8 Gy ex vivo. DNA damage induction (1 Gy 0.5 h) and repair (4 Gy 24 h) were assessed by duplicate γH2AX foci assays in 50-100 cells. Duplicate FLICA assays performed at 48 h post-8 Gy were employed as surrogate of radiation-induced apoptosis; %FLICA-positive cells were quantified by flow cytometry.Results: We observed limited intrapatient variation in γH2AX foci and %FLICA readouts; median difference of duplicate foci scores was - 0.37 (IQR = - 1.256-0.800) for 1 Gy 0.5 h and 0.09 (IQR = - 0.685-0.792) for 4 Gy 24 h; ICC of ≥0.80 was observed for duplicate %FLICA0Gy and %FLICA8Gy assays of CD4+ and CD8+ T lymphocytes. As expected, we observed wide inter-patient heterogeneity in both assays that was independent of intrapatient variation and clinical covariates, with the exception of age, which was inversely correlated with %FLICAbackground-corrected (Spearman R = - 0.406, P < 0.001 [CD4+]; R = - 0.220, P = 0.04 [CD8+]). Lastly, an exploratory case-control analysis indicates increased levels of γH2AX foci at 4 Gy 24 h in patients with severe late radiotherapy-induced xerostomia (P = 0.05).Conclusion: Here, we confirmed the technical reproducibility of DNA damage response assays for clinical implementation as biomarkers of clinical radiosensitivity in nasopharynx cancer patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on caries progression in irradiated nasopharyngeal carcinoma (NPC) patients. Methods: Twenty-one males and three females (median age, 50 years) were randomized into two groups before radiotherapy. Subjects had at least eight teeth after oral health clearance. The test group used 0.4 % stannous fluoride gel and a crème containing 10 % CPP-ACP daily; the control group used a similar crème without CPP-ACP and otherwise identical care. Subjects applied the crème three times daily and fluoride gel once daily. Caries status, saliva and plaque parameters were measured pre-radiotherapy, at 2 weeks and 3 months post-radiotherapy. Results: Baseline International Caries Detection and Assessment System (ICDAS) scores were 0-1126 surfaces (93.9 %), 1-28 surfaces (2.3 %), 2-40 surfaces (3.3 %) and 3-6 surfaces (0.5 %) for the control and 0-1186 surfaces (95.6 %), 1-31 surfaces (2.5 %), 2-15 surfaces (1.2 %) and 3-8 surfaces (0.7 %) for the test group. Twenty-two subjects returned at 3 months post-radiotherapy with reduced plaque pH, salivary flow, pH and buffering capacity. Nine test and 8 control subjects developed 32 and 59 new caries lesions, respectively. Test subjects showed lower caries progression than the controls: all surfaces (OR 0.51, 95 % CI 0.17∼1.59), occlusal (OR 0.20, 95 % CI 0.03∼1.29) and smooth surfaces (OR 0.61, 95 % CI 0.16∼2.38). The difference was not statistically significant. Conclusion: Application of CPP-ACP did not significantly reduce caries progression in NPC patients in the first 3 months after radiotherapy as compared to controls. Clinical relevance: Adjunct use of CPP-ACP with stannous fluoride gel in irradiated NPC patients gave comparable results compared to stannous fluoride gel alone in reducing caries progression. [ABSTRACT FROM AUTHOR]

BACKGROUND The current study was performed to report the long-term results of a trial comparing concurrent chemotherapy and radiotherapy (CCRT) with surgery and adjuvant radiotherapy (RT) in patients with stage III/IV nonmetastatic head and neck squamous cell carcinoma. METHODS Patients with stage III/IV resectable head and neck squamous cell carcinoma were randomized to surgery followed by RT or CCRT. The trial was halted prematurely due to poor accrual. Human papillomavirus status was tested on archival material using polymerase chain reaction sequencing. RESULTS Of the total of 119 patients, 60 patients were randomized to primary surgery (S arm) and 59 patients were randomized to CCRT (C arm). Human papillomavirus status was tested in 75 patients, and only 3 were found to be positive. The median follow-up for surviving patients was 13 years. Analysis of the entire cohort demonstrated no statistically significant difference in overall survival and disease-specific survival (DSS): 5-year rates were 45% versus 35% for overall survival ( P = .262) and 56% versus 46% for DSS ( P = .637) for the S arm and C arm, respectively. Analysis by subsites indicated that this difference favoring the S arm was mainly driven by survival data among patients with cancers of the oral cavity and maxillary sinus. For patients with oral cavity cancer, survival was significantly better in those who underwent primary surgery compared with CCRT; the 5-year DSS rate was 68% versus 12% for the S arm and C arm, respectively ( P = .038). For patients with cancers of the maxillary sinus, the 5-year DSS rate was 71% for patients on the S arm and 0% for patients on the C arm ( P = .05). CONCLUSIONS These long-term results demonstrate a significant advantage for primary surgery in patients with cancers of the oral cavity or maxillary sinus, providing strong support for primary surgery as the main modality of treatment for these subsites. In other subsites, CCRT and surgery with adjuvant RT were found to demonstrate similar efficacy for survival in patients with advanced resectable tumors. Cancer 2015;121:1599-1607. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Following the dispersal out of Africa, where hominins evolved in warm environments for millions of years, our species has colonised different climate zones of the world, including high latitudes and cold environments. The extent to which human habitation in (sub-)Arctic regions has been enabled by cultural buffering, short-term acclimatization and genetic adaptations is not clearly understood. Present day indigenous populations of Siberia show a number of phenotypic features, such as increased basal metabolic rate, low serum lipid levels and increased blood pressure that have been attributed to adaptation to the extreme cold climate. In this study we introduce a dataset of 200 individuals from ten indigenous Siberian populations that were genotyped for 730,525 SNPs across the genome to identify genes and non-coding regions that have undergone unusually rapid allele frequency and long-range haplotype homozygosity change in the recent past. At least three distinct population clusters could be identified among the Siberians, each of which showed a number of unique signals of selection. A region on chromosome 11 (chr11:66–69 Mb) contained the largest amount of clustering of significant signals and also the strongest signals in all the different selection tests performed. We present a list of candidate cold adaption genes that showed significant signals of positive selection with our strongest signals associated with genes involved in energy regulation and metabolism (CPT1A, LRP5, THADA) and vascular smooth muscle contraction (PRKG1). By employing a new method that paints phased chromosome chunks by their ancestry we distinguish local Siberian-specific long-range haplotype signals from those introduced by admixture. [ABSTRACT FROM AUTHOR]

Background: In randomised clinical trials involving time-to-event outcomes, the failures concerned may be events of an entirely different nature and as such define a classical competing risks framework. In designing and analysing clinical trials involving such endpoints, it is important to account for the competing events, and evaluate how each contributes to the overall failure. An appropriate choice of statistical model is important for adequate determination of sample size.Methods: We describe how competing events may be summarised in such trials using cumulative incidence functions and Gray's test. The statistical modelling of competing events using proportional cause-specific and subdistribution hazard functions, and the corresponding procedures for sample size estimation are outlined. These are illustrated using data from a randomised clinical trial (SQNP01) of patients with advanced (non-metastatic) nasopharyngeal cancer.Results: In this trial, treatment has no effect on the competing event of loco-regional recurrence. Thus the effects of treatment on the hazard of distant metastasis were similar via both the cause-specific (unadjusted csHR = 0.43, 95% CI 0.25 - 0.72) and subdistribution (unadjusted subHR 0.43; 95% CI 0.25 - 0.76) hazard analyses, in favour of concurrent chemo-radiotherapy followed by adjuvant chemotherapy. Adjusting for nodal status and tumour size did not alter the results. The results of the logrank test (p = 0.002) comparing the cause-specific hazards and the Gray's test (p = 0.003) comparing the cumulative incidences also led to the same conclusion. However, the subdistribution hazard analysis requires many more subjects than the cause-specific hazard analysis to detect the same magnitude of effect.Conclusions: The cause-specific hazard analysis is appropriate for analysing competing risks outcomes when treatment has no effect on the cause-specific hazard of the competing event. It requires fewer subjects than the subdistribution hazard analysis for a similar effect size. However, if the main and competing events are influenced in opposing directions by an intervention, a subdistribution hazard analysis may be warranted. [ABSTRACT FROM AUTHOR]

Background. The aim of this study was to review our experience and demonstrate the safety of intracavitary brachytherapy (ICB) in patients with nasopharyngeal carcinoma (NPC). Methods. Hundred seventy-eight patients with early T1-2b disease underwent radical external beam radiation therapy (EBRT) followed by ICB boost. The primary tumor received 66 Gy of EBRT over 33 fractions using 6 or 10 MV photons. ICB insertions were performed 1 week later, delivering 10 Gy in 2 fractions over 8 days. Kaplan-Meier survival analyses were used to calculate the actuarial 5-year overall survival (OS), cause-specific survival, local control, and disease-free survival (DFS). Results. Five-year local control rates were 91.6%. OS, DFS, and cause-specific survival were estimated to be 85.25%, 81.7%, and 87.9%, respectively. Median follow-up was 86 months. There were no documented serious complications noted with ICB. Conclusion. ICB boost supplementing radical EBRT is an excellent method of enhancing local control for patients with NPC with early T1-2b disease. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [ABSTRACT FROM AUTHOR]

Background Retropharyngeal lymph node (RLN) staging in nasopharyngeal carcinoma (NPC) can be controversial. Methods We retrospectively reviewed all patients with T2–4, N0–1 NPC treated between 1992 and 1994 to examine if RLN metastasis resulted in an increased incidence of distant metastases. Results Of the 667 patients with NPC, 395 had T2–4, N0–1 disease, 140 had N0, and 255 had N1. All had staging CT scans and were treated with radiotherapy. Median follow-up was 8.3 years. Seventy-four percent showed undifferentiated histology. In this cohort, 187 (47%) had RLN metastases. Multivariate analysis showed that RLN conferred a higher hazard for distant metastasis (p = .04). Using the Kaplan–Meier method, patients with N0 disease and RLN had a similar hazard for distant metastases as patients with N1 disease when compared with patients with N0 disease and without RLN. Conclusion Patients with N0 disease and RLN appear to share a similar prognosis to patients with N1 disease. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [ABSTRACT FROM AUTHOR]

The article focuses on the treatment of nasopharyngeal carcinoma (NPC) which is highly reactive to several chemotherapeutic agents. A three-drug combination chemotherapy, which constitutes of gemcitabine, paclitaxel, and carboplatin, was proposed to treat patients with metastatic NPC. In the study of 28 patients, it notes that toxicities generally came from bone marrow suppression including neutropenia, anemia, and thrombocytopenia.

Background.We sought to assess the efficacy and complications of linear accelerator-based stereotactic radiosurgery (SRS) plus intracavitary irradiation (ICI) as salvage treatment for local persistent and recurrent nasopharyngeal carcinoma (NPC) after primary external beam radiotherapy (EBRT). Methods.Between July 1995 and June 2003, 36 patients (25 men and 11 women; median age, 48 years; range, 22–66 years) with local recurrent NPC confined to the nasopharynx (rT1) or limited extension to the parapharynx and nasal cavity (rT2) were treated with SRS plus ICI. Nineteen patients had rT1 and 17 had rT2 disease. Five patients (13.8%) had persistent disease, and 31 patients (86.1%) had recurrent disease using the definition of >4 months after the primary treatment as recurrent relapse. The median target volume was 36.3 cm3 (range, 10.3–56.2 cm3) for the SRS treatment. All patients received 18 Gy to the 90% isodose line followed by two separate ICI 6 Gy each to 0.5 cm from the surface of the endotracheal balloon. Patients were assessed with serial nasoendoscopy and repeat scans (CT or MRI) at 3 months, and suspicious lesions were rebiopsied. Results.The median follow-up for surviving patients was 4.24 years (range, 0.73–8.81 years). Twenty-two of 36 (61%) patients were alive at the time of reporting. Twenty patients were free of disease, and two patients were alive with disease. Fourteen of 36 (39%) patients had died (five of distant metastases, six of local recurrences, two of both local disease and distant metastases, and one of unrelated cause). Patients with rT1 disease (median survival not reached) fared better that patients with rT2 disease (median survival, 4.6 years). The actuarial 5-year disease-free survival and overall survival (OS) were 57% (rT1 78%, rT2 39%) and 62% (rT1 80%, rT2 48%), respectively. The actuarial 5-year local control was 65% (rT1 82%, rT2 49%). The treatment was well tolerated with no significant acute complications. Sixteen patients (44%) had late complications, including palatal fibrosis in six patients (17%), trismus in seven patients (20%), cranial nerve palsies in seven patients (20%), temporal lobe necrosis in two patients (8%), and osteoradionecrosis of the skull base in six patients (17%). The complication-free survival rates at 2 and 5 years were 70% (95% confidence interval [CI], 56% to 87%) and 31% (95% CI, 17% to 56%), respectively. No patient died as a direct result of the late complication. Conclusion.Although our series is small, the combination of SRS and ICI seems to be an effective salvage treatment for early-stage recurrent NPC. The OS of 62% at 5 years is very encouraging and favorable compared with reported reirradiation or surgical series. The late complications are considerable but expected because of the high doses of radiation previously delivered. The ideal dose fractionation for SRS and ICI is unknown and remains to be defined. © 2005 Wiley Periodicals, Inc. Head Neck28: 321–329, 2006 [ABSTRACT FROM AUTHOR]

Background: In methodological studies and outcomes research, questionnaires often comprise several health-related quality of life (HRQoL) measures. Previous psychological studies have suggested that changing the sequential order of measurement scales within a questionnaire could alter the pattern of responses. Yet, information on the presence or absence of order effects on the assessment of HRQoL in cancer patients is limited. Methods: An incomplete block design was used in this study of 1277 cancer patients. Each patient filled out a questionnaire package that contained two of the three major cancer-specific HRQoL instruments, namely the Functional Assessment of Cancer Therapy - General, the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire and the Functional Living Index - Cancer. Within a questionnaire package the sequential order of the instruments contained were randomised. Measurement properties of the instruments, including the number of missing values, mean HRQoL scores, known-groups validity and internal consistency were compared between samples of different presentation orders. Results: No effect of presentation order on the four properties aforementioned was found. Conclusion: Presentation order is unlikely to alter the responses to these HRQoL instruments administered in cancer patients when any two of them are used together. [ABSTRACT FROM AUTHOR]

Docetaxel has a response rate of greater than 30% in first-line treatment of Western patients with advanced non-small cell lung cancer (NSCLC). The goal of this open-label, phase II study was to evaluate the activity and safety profile of docetaxel in Asian patients with inoperable untreated stage III NSCLC. Docetaxel was given at 100 mg/m[sup 2] as a 1-h infusion every 3 weeks. Prophylactic dexamethasone was given to reduce hypersensitivity reactions and edema. Thirty-five patients were enrolled in the study. The response rate was 34% (95% CI, 19%-50%) according to intent-to-treat analysis. No complete response was observed. Twenty-four patients (69%) had grade 3 or 4 neutropenia in cycle 1, and febrile neutropenia was seen in 12 patients. Six patients (17%) experienced mild fluid retention. Docetaxel is an active agent in first-line treatment of Asian patients with locally advanced NSCLC, with the main toxicity being neutropenia. Fluid retention was a minor problem in this study. [ABSTRACT FROM AUTHOR]

The favourable experience with the combination regimen of vinorelbine, ifosfamide and cisplatin (NIP) in patients with metastatic non-small cell lung cancer (NSCLC) has led to a protocol assessing this regimen as an induction treatment in patients with stage III unresectable NSCLC, followed by thoracic radiotherapy with concurrent daily cisplatin as a radiosensitizer. Two cycles of NIP were administered 21 days apart; each cycle comprised i.v. vinorelbine 25 mg/m[sup 2] on days 1 and 8, i.v. ifosfamide 3 g/m[sup 2] on day 1 with MESNA as uroprotection, and i.v. cisplatin 50 mg/m[sup 2] on day 1. Radical thoracic radiotherapy commenced on day 43 to a total dose of 64 Gy and i.v. cisplatin 6 mg/m[sup 2] was given concurrently prior to each fraction of radiation as a sensitiser. Two more cycles of NIP were given to patients who responded favourably to the induction treatment about 2 weeks after completion of radiation. Between July 1995 and July 1997, 44 patients were treated with this protocol. This treatment schedule was generally well tolerated. Grade 3-4 neutropenia occurred in 50% of the patients and neutropenic sepsis was seen in 8. Grade 3-4 oesophagitis was uncommon. Most of the patients were able to complete the induction and concurrent chemoradiotherapy phase. Major response occurred in 75% of the patients with 2 (4.5%) complete responses (CR). A total of 6 patients achieved CR after chemoradiotherapy. At a median follow-up of 35 months, the median overall survival for all patients was 15 months with a 3-year survival rate of 24%. The median overall survival for stage IIIA patients was 19 months with a 3-year survival rate of 39% in contrast to 13 months' median overall survival and only 15% 3-year survival rate for stage IIIB. The NIP regimen results in a high response rate in NSCLC and this treatment programme seems to benefit selected patients with stage III disease. [ABSTRACT FROM AUTHOR]

Between September 1994 and July 1997, 78 patients with advanced/metastatic, non-small cell lung cancer (NSCLC) were selected for the NIP (vinorelbine, ifosfamide, and cisplatin) protocol. The study group included 43 males; age range 34-74 years; median age 56 years; median follow-up for all patients was 14 months and for surviving patients, 30 months. Histological distribution included 55 adenocarcinomas (70.5%), 8 squamous cell carcinomas, and 9 large cell carcinomas. Stage distribution was 14 stage IIIB (malignant effusions) and 64 stage IV or recurrent metastatic; sites of metastasis were lungs, -26; liver-19; bones-27; brain-7; adrenals-3; distant nodes-2; skin-2. The NIP regimen was well tolerated by most of the patients but nausea/vomiting was noted in 55% of the cycles administered, most of them of grade 1-2 severity. Fifteen neutropenic episodes (5%) were encountered. Response to NIP was: 44 partial responses (56%); 1 complete response (1%); overall response, 58%. For stage IIIB, overall response was 36%, while for stage IV/metastatic, overall response was 63%. The median time to progression was 7 months for stage IIIB and 8 months for stage IV/metastatic disease and the overall median survival achieved was 14 months, with 60% of patients alive after one year. No significant difference in survival outcome was noted between patients with metastatic disease and those with stage IIIB (malignant effusion) disease. The NIP regimen has produced encouraging results in advanced NSCLC, as well as a favourable toxicity profile. The efficacy of NIP as a palliative tool should be assessed. A randomized trial to compare NIP with a two-drug combination of vinorelbine and cisplatin has been initiated. [ABSTRACT FROM AUTHOR]

Radiomics pipelines have been developed to extract novel information from radiological images, which may help in phenotypic profiling of tumours that would correlate to prognosis. Here, we compared two publicly available pipelines for radiomics analyses on head and neck CT and MRI in nasopharynx cancer (NPC). 100 biopsy-proven NPC cases stratified by T- and N-categories were enrolled in this study. Two radiomics pipeline, Moddicom (v. 0.51) and Pyradiomics (v. 2.1.2) were used to extract radiomics features of CT and MRI. Segmentation of primary gross tumour volume was performed using Velocity v. 4.0 by consensus agreement between three radiation oncologists. Intraclass correlation between common features of the two pipelines was analysed by Spearman's rank correlation. Unsupervised hierarchical clustering was used to determine association between radiomics features and clinical parameters. We observed a high proportion of correlated features in the CT data set, but not for MRI; 76.1% (51 of 67 common between Moddicom and Pyradiomics) of CT features and 28.6% (20 of 70 common) of MRI features were significantly correlated. Of these, 100% were shape-related for both CT and MRI, 100 and 23.5% were first-order-related, 61.9 and 19.0% were texture-related, respectively. This interpipeline heterogeneity affected the downstream clustering with known prognostic clinical parameters of cTN-status and GTVp. Nonetheless, shape features were the most reproducible predictors of clinical parameters among the different radiomics modules. Here, we highlighted significant heterogeneity between two publicly available radiomics pipelines that could affect the downstream association with prognostic clinical factors in NPC The present study emphasized the broader importance of selecting stable radiomics features for disease phenotyping, and it is necessary prior to any investigation of multicentre imaging datasets to validate the stability of CT-related radiomics features for clinical prognostication. [ABSTRACT FROM AUTHOR]

Humans have more copies of amylase genes than other primates. It is still poorly understood, however, when the copy number expansion occurred and whether its spread was enhanced by selection. Here we assess amylase copy numbers in a global sample of 480 high coverage genomes and find that regions flanking the amylase locus show notable depression of genetic diversity both in African and non-African populations. Analysis of genetic variation in these regions supports the model of an early selective sweep in the human lineage after the split of humans from Neanderthals which led to the fixation of multiple copies of AMY1 in place of a single copy. We find evidence of multiple secondary losses of copy number with the highest frequency (52%) of a deletion of AMY2A and associated low copy number of AMY1 in Northeast Siberian populations whose diet has been low in starch content. [ABSTRACT FROM AUTHOR]

Background: Over-expression of cyclooxygenase-2 (COX-2) enzyme has been reported in nasopharyngeal carcinoma (NPC). However, the prognostic significance of this has yet to be conclusively determined. Thus, from our randomized trial of radiation versus concurrent chemoradiation in endemic NPC, we analyzed a cohort of tumour samples collected from participants from one referral hospital.Methods: 58 out of 88 patients from this institution had samples available for analysis. COX-2 expression levels were stratified by immunohistochemistry, into negligible, weak, moderate and strong, and correlated with overall and disease specific survivals.Results: 58% had negligible or weak COX-2 expression, while 14% and 28% had moderate and strong expression respectively. Weak COX-2 expression conferred a poorer median overall survival, 1.3 years for weak versus 6.3 years for negligible, 7.8 years, strong and not reached for moderate. There was a similar trend for disease specific survival.Conclusion: Contrary to literature published on other malignancies, our findings seemed to indicate that over-expression of COX-2 confer a better prognosis in patients with endemic NPC. Larger studies are required to conclusively determine the significance of COX-2 expression in these patients. [ABSTRACT FROM AUTHOR]